EB - Risk factors of metal health disorders II Flashcards
What are some environmental risk factors for mental health disorders? (6)
- Physical health challenges (Gut-brain axis).
- Social and economic stressors (e.g., deprivation, inequality, crime, pollution).
- Early life experiences (e.g., prenatal exposures, adversity, bullying).
- Infections & obstetric complications
- Substance use & abuse.
- Natural disasters.
^Trigger stress responses
What 2 CNS disorders require environmental exposure for diagnosis?
- PTSD.
- Substance use disorder
What is a transdiagnostic factor?
A psychological process or mechanism that cuts across different mental health disorders. It’s a common thread that links seemingly disparate conditions.
How does stress act as a transdiagnostic factor in mental health? (5)
- Cuts across anxiety, mood, and trauma-related disorders.
- Maladaptive responses to stress are central to the development of these disorders.
- Supports the ‘Diathesis-Stress Hypothesis’ - A combination of genetic predisposition and adversity leads to psychopathology.
- Allostatic load - cumulative life stress increases vulnerability
- Critical periods of development - When stress has disproportionate effects leading to long-lasting effects on mental health
What is early life stress/adversity? (2)
- A Critical period for brain development
- When the brain highly sensitive to adverse experiences in early life
What are the two domains of early life stress (ELA)?
Deprivation: Includes neglect, poverty, and institutionalization.
Threat: Includes sexual, emotional, physical abuse, war, and natural disasters.
How does early life stress (ELA) affect mental health? (9)
-
Increases risk of:
Cognitive impairments.
Substance use disorders.
Depression disorders
Anxiety disorders
Schizophrenia
Suicide risk -
Predictor of:
Recurrent episodes
Severity
Resistance to treatment.
How are rodent models used to study early life stress? (3)
Analyse effects of:
- Natural variations in maternal care.
- Maternal separation.
- Limited bedding and nesting environments.
How are Non-human primate models used to study early life stress? (2)
Analyse effects of:
- Natural variations in maternal care
- Variable foraging demand (e.g., inconsistent availability of food resources).
What do rodent and non-human primate models have an effect on? (4)
- Brain wiring
- Epigenetics
- Gut-brain axis
- Metabolic changes
How does early life adversity (ELA) impact inhibitory interneurons? (2)
- ELA causes shifts in the timing of inhibitory interneuron processes, occurring slightly earlier than in normal development.
- This disruption affects critical periods of brain plasticity, potentially leading to imbalances in excitation and inhibition in the brain.
How does early life adversity (ELA) affect serotonergic input? (2)
- ELA reduces serotonergic (5-HT) input during development.
- Lower serotonin signaling increases susceptibility to anxiety and depression later in life.
Which brain regions are affected by early life adversity (ELA)? (5)
- Prefrontal Cortex (PFC): Impaired cognition and fear extinction, increased anxiety/depression.
- Hippocampus: Impaired memory, increased fear generalisation and anxiety/depression.
- Amygdala: Altered fear behavior, increased anxiety/depression, reduced input from mPFC
- Hypothalamic-pituitary-adrenal (HPA Axis): Impaired stress response.
- Raphe nuclei: increased anxiety/depression
What are some cellular changes caused by ELA? (6)
- Synaptic pruning: Disrupted, leading to less refined connections.
- Microglia function: Dysregulated activation affects brain immunity.
- Dendritic branching: Impaired development reduces neuronal complexity.
- Myelination: Impaired, slower communication between neurons.
- Neurogenesis: Reduced, especially in the hippocampus.
- GR function: Impaired glucocorticoid receptor response increases stress vulnerability.
What is the function of the (HPA) axis? (4)
- The HPA axis regulates homeostatic mechanisms by responding to stress:
- Hypothalamus (PVN): Releases CRH (corticotropin-releasing hormone).
- Anterior Pituitary: CRH stimulates the secretion of ACTH into systemic circulation.
- Adrenal Cortex: ACTH promotes synthesis and release of glucocorticoids.
How do glucocorticoids exert their effects in the body? (2)
- Glucocorticoids bind to their receptors (MRs and GRs) in various organs, including the brain.
- Once bound, these receptors translocate to the nucleus, causing changes in gene transcription and protein translation.
How is the HPA axis dysregulated by early life stress (ELS)? (3)
- Reduced GR expression impairs feedback, increasing stress reactivity.
- ELS resets the HPA axis, leading to heightened stress responses in adulthood.
- Evidence: Rat models show that low maternal care increases corticosterone levels and stress response.
What are the epigenetic effects of low maternal care in models? (4)
- Increased DNA methylation at the Nr3c1 gene (encodes GR).
- Reduced histone acetylation, decreases transcription factor binding.
- Decreased GR mRNA and protein expression.
- Effects reversible with HDAC inhibitors, suggesting a potential therapeutic approach.
How does ELS affect the reward system?
- Alters gene expression in the Ventral Tegmental Area (VTA).
- ELS combined with adult stress (e.g., STVS) leads to unique transcriptional changes, impacting neuron differentiation, ion transport, and stress resilience.
- ELS combined with STVS significantly increases the latency to eat, indicating heightened stress or anxiety-like behavior
How does the immune system influence neurodevelopmental disorders? (3)
- Maternal prenatal infection: Strong risk factor for schizophrenia, autism, ADHD, Tourette syndrome, and BPD.
- Postnatal immune system: Also plays a role in shaping susceptibility to ASD.
- Maternal Immune Activation (MIA) Model: Used to study how immune activation during pregnancy impacts brain development.
How does the gut-brain axis influence neuropsychiatric disorders? (3)
- Links diet, gut microbiota, and brain health.
- Specific metabolites like 4EPS (comes from gut flora) can cross the blood-brain barrier and modulate neural networks.
- Example: Elevated 4EPS in ASD correlates with anxiety-like behavior, which can be mitigated using GI-restricted treatments like AB-2004.
What are the benefits of targeting the microbiota-gut-brain axis in CNS disorders? (3)
- Early diagnosis and stratification.
- Avoids systemic side effects as treatments don’t need to cross the blood-brain barrier.
- Offers novel therapeutic options for conditions like ASD and anxiety.
